Association of residential greenness, air pollution with adverse birth outcomes: Results from 61,762 mother‑neonatal pairs in project ELEFANT (2011-2021).

Background: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes.

Methods: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA.

Association between diesel exhaust exposure and mitochondrial DNA methylation.

Objectives: Diesel exhaust is an established human carcinogen, however the mechanisms by which it leads to cancer development are not fully understood. Mitochondrial dysfunction is an established contributor to carcinogenesis. Recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis.

Genomic targets and selective inhibition of DNA methyltransferase isoforms.

Background: DNA methylation in the human genome is established and maintained by DNA methyltransferases (DNMTs). DNMT isoforms show differential expression by cell lineage and during development, but much remains to be elucidated about their shared and unique genomic targets.

Results: We examined changes in the epigenome following overexpression of 13 DNMT isoforms in HEK293T cells.

Association between mitochondrial DNA methylation and internal exposure to polycyclic aromatic hydrocarbons (PAHs), nitrated-PAHs (NPAHs) and oxygenated-PAHs (OPAHs) in young adults from Tianjin, China.

Polycyclic aromatic hydrocarbons (PAHs), nitrated-PAHs (NPAHs) and oxygenated-PAHs (OPAHs) are environmental pollutants with adverse effects on human health. The correlation between the concentrations of PAHs, NPAHs and OPAHs in human plasma and the methylation level of mitochondrial DNA (mtDNA) was investigated using data from 110 plasma samples collected in Tianjin, China. The median concentrations of PAHs, NPAHs and OPAHs were 16.

The exposure levels and health risk assessment of antibiotics in urine and its association with platelet mitochondrial DNA methylation in adults from Tianjin, China: A preliminary study.

There has been extensive research on antibiotics exposure in adults by biomonitoring, but the biological mechanisms and potential risks to human health remain limited. In this study, 102 adults aged 26-44 years in Tianjin were studied and 23 common antibiotics in urine were analyzed by Liquid chromatography-mass spectrometry (LC-MS). All antibiotics were detected in urine, with an overall detection frequency of 40.

Associations of adverse pregnancy outcomes with high ambient air pollution exposure: Results from the Project ELEFANT.

Background: Investigations on the potential effects of high air pollution exposure before pregnancy on adverse pregnancy outcomes are limited, and it is unknown whether air quality standards looser than that set by World Health Organization (WHO) still can provide sufficient protection pregnant women from adverse pregnancy outcomes.

Objectives: To evaluate the potential effects of high ambient air pollution around pregnancy on preterm birth (PTB) and low birth weight (LBW), and assess the risk of PTB and LBW associated with air pollutants with reference to different air quality standards of WHO and China.

Methods: Our study leveraged 10,960 pregnant women from the Project ELEFANT.

Environmental epitranscriptomics.

Chemical modifications of RNA molecules have gained increasing attention since evidence emerged for their substantive roles in a range of biological processes, such as the stability and translation of mRNA transcripts. More than 150 modifications have been identified in different organisms to date, collectively known as the 'epitranscriptome', with 6-methyladenosine (mA), 5-methylcytidine (mC), pseudouridine and N1-methyladenosine (mA) the most extensively investigated. Although we are just beginning to elucidate the roles of these modifications in cellular functions, there is already evidence for their dysregulation in diseases such as cancer and neurodevelopmental disorders.

Prenatal PM exposure and the risk of adverse births outcomes: Results from Project ELEFANT.

Background: Studies investigating the impact of fine particulate matter (PM) exposure during pregnancy upon adverse birth outcomes have primarily been performed in Western nations with low ambient PM levels. We examined associations between high levels of PM exposure during pregnancy and risk of adverse birth outcomes by timing and level of exposure in a Chinese population.

Methods: We analysed data from 10,738 live births within the Project ELEFANT study based in Tianjin, China.

Mitochondrial DNA methylation in placental tissue: a proof of concept study by means of prenatal environmental stressors.

While previous studies have demonstrated that prenatal exposure to environmental stressors is associated with mitochondrial DNA (mtDNA) methylation, more recent investigations are questioning the accuracy of the methylation assessment and its biological relevance. In this study, we investigated placental mtDNA methylation while accounting for methodological issues such as nuclear contamination, bisulphite conversion, and PCR bias. From the ENVIRAGE birth cohort, we selected three groups of participants (n = 20/group).

DNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes.

The identification of early markers of dementia is important for higher-risk populations such as those with type 2 diabetes (T2D). Retrotransposons, including long interspersed nuclear element 1 (LINE-1) and Alu, comprise ~40% of the human genome. Although dysregulation of these retrotransposons can induce aberrant gene regulation and genomic instability, their role in the development of pre-symptomatic dementia (PSD) among T2D patients is unknown.

Elevated serum mitochondrial DNA in females and lack of altered platelet mitochondrial methylation in patients with Parkinson´s disease.

Mitochondrial dysfunction has long been considered in the pathogenesis of Parkinson's disease (PD). This is evident from the presence of mitochondrial DNA deletions in substantia nigra neurons and respiratory chain abnormalities in the skeletal muscle of PD patients. However, the contributing factors that potentially cause oxidative stress in PD are still elusive.

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity.

Background: The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity.

Methods: We devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free.

Analysis of retrotransposon subfamily DNA methylation reveals novel early epigenetic changes in chronic lymphocytic leukemia.

Retrotransposons such as LINE-1 and Alu comprise >25% of the human genome. While global hypomethylation of these elements has been widely reported in solid tumours, their epigenetic dysregulation is yet to be characterised in chronic lymphocytic leukaemia, and there has been scant consideration of their evolutionary history that mediates sensitivity to hypomethylation. Here, we developed an approach for locus- and evolutionary subfamily-specific analysis of retrotransposons using the Illumina Infinium Human Methylation 450K microarray platform, which we applied to publicly-available datasets from chronic lymphocytic leukaemia and other haematological malignancies.

Exposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes.

The epitranscriptome comprises more than 100 forms of RNA modifications. Of these, N6-methyladenosine (mA) is the most abundantform of RNA methylation, with roles in modulating mRNA transcript processing and regulation. The aims of the study weretoexamine changes inmA RNA methylation in A549 lung epithelial cells in response to environmental toxicants, anddifferential gene expression of mA modulator genes ('readers', 'writers' and 'erasers') in human subjects exposed toparticulate matter (PM) and in lung cancer tissueusing publicly-available microarray datasets.

Occupational noise exposure is associated with hypertension in China: Results from project ELEFANT.

Objectives: We investigated the association between occupational noise exposure and the risk of elevated blood pressure and hypertension by stage in young adults.

Methods: We utilized 124,286 young adults (18-40 years) from the Project ELEFANT study. We categorized occupational noise exposure as high (75 dBA noise exposure for more than 4 hours per day) or low, and measured blood pressure (mmHg) and categorized participants by hypertension stage (normal, elevated, Stage 1, Stage 2).

Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT.

Background: The menstrual cycle is regulated by reproductive hormones such as estrogen which has been implicated in the pathogenesis of hypertension and is associated with obesity. However, to date there has scant study of hypertension in relation to menstrual characteristics and abnormalities. We hypothesize that adverse menstrual characteristics are associated with an increase the prevalence of hypertension and that this relationship is exacerbated by obesity.

Age at menarche and prevention of hypertension through lifestyle in young Chinese adult women: result from project ELEFANT.

Background: Early and late age at menarche are associated with risk of hypertension, but little is known whether modifiable lifestyle can reduce this risk.

Methods: Our study leverages 60,135 healthy young Chinese women from the Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) study. Menarche age and lifestyle factors were assessed by self-reported questionnaires and hypertension was diagnosed by physicians.

Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock.

Scope: Alterations in DNA methylation patterns are correlated with aging, environmental exposures, and disease pathophysiology; the possibility of reverting or preventing these processes through dietary intervention is gaining momentum. In particular, methyl donors that provide S-adenosyl-methionine for one-carbon metabolism and polyphenols such as flavanols that inhibit the activity of DNA methyltransferases (DNMTs) can be key modifiers of epigenetic patterns.

Methods And Results: DNA methylation patterns are assessed in publicly available Illumina Infinium 450K methylation datasets from intervention studies with either folic acid + vitamin B12 (GSE74548) or monomeric and oligomeric flavanols (MOF) (GSE54690) in 44 and 13 participants, respectively.

Psychosocial stress is associated with benign breast disease in young Chinese women: results from Project ELEFANT.

Purpose: Psychosocial stress, including bereavement and work-related stress, is associated with the risk of breast cancer. However, it is unknown whether it may also be linked with increased risk of benign breast disease (BBD).

Methods: Our study leveraged 61,907 women aged 17-55 years old from the Project ELEFANT study.

Pesticide use and LINE-1 methylation among male private pesticide applicators in the Agricultural Health Study.

Cancer risk may be associated with DNA methylation (DNAm) levels in Long Interspersed Nucleotide Element 1 (LINE-1), a surrogate for global DNAm. Exposure to certain pesticides may increase risk of particular cancers, perhaps mediated in part through global DNAm alterations. To date, human data on pesticide exposure and global DNAm alterations are limited.

Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture.

Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways.

The effect of morphine upon DNA methylation in ten regions of the rat brain.

Morphine is one of the most effective analgesics in medicine. However, its use is associated with the development of tolerance and dependence. Recent studies demonstrating epigenetic changes in the brain after exposure to opiates have provided insight into mechanisms possibly underlying addiction.

Promoter methylation status in genes related with inflammation, nitrosative stress and xenobiotic metabolism in low-level benzene exposure: Searching for biomarkers of oncogenesis.

Unlabelled: Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we studied promoter DNA methylation of IL6, CYP2E1 and iNOS in blood cells from three groups of workers: a) gas station attendants (GS) exposed to low levels of benzene; b) plastic shoe factory workers (PS) exposed to other solvents different to benzene and c) administrative workers as a reference group with no solvent exposure (C).

Impact of Chromosomal Rearrangement upon DNA Methylation Patterns in Leukemia.

Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the translocation t(9:22), in establishing DNA methylation profiles in cancer.